Combining the Physical–Chemical Approach with Standard Base Excess to Understand the Compensation of Respiratory Acid–Base Derangements: An Individual Participant Meta-analysis Approach to Data from Multiple Canine and Human Experiments

Abstract

Background. Several studies explored the interdependence between PaCO2 and bicarbonate during respiratory acid-base derangements. We aimed to reframe the bicarbonate adaptation to respiratory disorders according to the physical-chemical approach, hypothesizing that (i) bicarbonate concentration during respiratory derangements is associated with strong ion difference; (ii) during acute respiratory disorders, strong ion difference changes are not associated with standard base excess. Methods. This is an individual participant data meta-analysis from multiple canine and human experiments published up to April 29, 2021. Studies testing the effect of acute or chronic respiratory derangements and reporting the variations of PaCO2, bicarbonate, and electrolytes were analyzed. Strong ion difference and standard base excess were calculated. Results. Eleven studies were included. PaCO2 ranged between 21 and 142 mmHg, while bicarbonate and strong ion difference ranged between 12.3 and 43.8 mmol/L, and 32.6 and 60.0 mEq/L, respectively. Bicarbonate changes were linearly associated with the strong ion difference variation in acute and chronic respiratory derangement (β-coefficient 1.2, 95%-CI 1.2 to 1.3, p<0.001). In the acute setting, sodium variations justified approximately 80% of strong ion difference change, while a similar percentage of chloride variation was responsible for chronic adaptations. In the acute setting, strong ion difference variation was not associated with standard base excess changes (β-coefficient -0.02, 95%-CI -0.11 to 0.07, p=0.719), while a positive linear association was present in chronic studies (β-coefficient 1.04, 95%-CI 0.84 to 1.24, p<0.001). Conclusions. The bicarbonate adaptation that follows primary respiratory alterations is associated with variations of strong ion difference. In the acute phase, the variation in strong ion difference is mainly due to sodium variations and is not paralleled by modifications of standard base excess. In the chronic setting, strong ion difference changes are due to chloride variations and are mirrored by standard base excess.

Respiratory Changes and Acid–Base Compensation: Watch the Salt

“…This unifies analyzing metabolic acid-base status with routine plasma chemistry and can be used in the operating room in a Bedside Stewart approach. 6,8 Zadek et al 3 found that, during acute changes in Paco 2 , the standard base-excess was almost unchanged. This is consistent with an article from 25 yr ago by Schlichtig et al 9 that has also been underappreciated until recently promoted in the New England Journal of Medicine.…”

“…A recent study of six volunteers undergoing hyperacute hyperventilation also found a 5 mEq/L decrease in strong ion difference but with a greater role for chloride than found by Zadek et al Reasons for these differences may include the nature of participants, assays, and type of hyperventialtion. 10 In contrast to minimal Na-Cl changes in acute respiratory changes, Zadek et al 3 found that, in chronic respiratory changes with the same increase in Paco 2 from 20 to 80 mmHg, the strong ion difference increased by 16 mM, a fourfold difference from acute changes. Again, there were small increases in sodium but they were supplemented by marked decreases in chloride, accounting for 80% of the increase in strong ion difference.…”

“…2 This high-altitude ABG is an extreme example of chronic respiratory alkalosis and associated metabolic (nonrespiratory) compensation. In this issue of Anesthesiology, Zadek et al 3 report a sophisticated individual participant meta-analysis of physiologic studies of metabolic compensation to acute and chronic respiratory change conducted during the past 60 yr. Their findings reinforce existing ideas and provide new insights into the scientific foundations of anesthesiology.…”

“…Combining the data from Zadek et al 3 and Schlichtig et al, 9 The important new information comes from analyzing changes in the concentrations of plasma sodium and chloride and the differences between the concentrations of these strong ions. Zadek et al 3 found that, in acute respiratory acidosis alkalosis, 80% of the small compensating change in strong ion difference was due to changes in plasma concentration. Increasing Paco 2 from 20 mmHg in acute respiratory alkalosis through to 80 mmHg in acute respiratory acidosis the Na-Cl strong ion difference only increased by 4 mEq/L.…”

“…As the opening quote reminds us, acid–base change is common in anesthesiology care, with any patient with an end-tidal p co 2 greater than 40 mmHg likely to have acute respiratory acidosis. However, rather than focusing only on renal compensatory changes in bicarbonate secondary to changes in Pa co 2 4,5 the researchers 3 have also focused on changes in both bicarbonate and standard base-excess, the latter being a practical tool 4,5 for assessing metabolic acid–base status that is underappreciated and underused. Zadek et al 3 have also gone a step further by examining changes in the two principal strong (completely dissociated) ions in plasma: sodium and chloride, which are central to the Stewart physicochemical approach to acid–base disorders.…”